12-123298103-T-C

Variant names:

• chr12-123298103-T-C
• rs868064117
• NM_001167856.3:c.3914A>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001167856.3(SBNO1):​c.3914A>G​(p.Tyr1305Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SBNO1 NM_001167856.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.55
• Publications: 0 publications found

Genes affected

SBNO1 (HGNC:22973): (strawberry notch homolog 1) Predicted to enable chromatin DNA binding activity and histone binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.862

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SBNO1	NM_001167856.3	c.3914A>G	p.Tyr1305Cys	missense_variant	Exon 31 of 32	ENST00000602398.3	NP_001161328.1
SBNO1	NM_018183.5	c.3911A>G	p.Tyr1304Cys	missense_variant	Exon 31 of 32		NP_060653.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SBNO1	ENST00000602398.3	c.3914A>G	p.Tyr1305Cys	missense_variant	Exon 31 of 32	5	NM_001167856.3	ENSP00000473665.1
SBNO1	ENST00000420886.6	c.3914A>G	p.Tyr1305Cys	missense_variant	Exon 30 of 31	1		ENSP00000387361.2
SBNO1	ENST00000267176.8	c.3911A>G	p.Tyr1304Cys	missense_variant	Exon 31 of 32	5		ENSP00000267176.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3914A>G (p.Y1305C) alteration is located in exon 30 (coding exon 30) of the SBNO1 gene. This alteration results from a A to G substitution at nucleotide position 3914, causing the tyrosine (Y) at amino acid position 1305 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T;.;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.99	D;D;.
M_CAP	Benign	0.068	D
MetaRNN	Pathogenic	0.86	D;D;D
MetaSVM	Uncertain	0.24	D
MutationAssessor	Benign	1.7	L;.;L
PhyloP100		2.6
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-4.7	D;D;.
REVEL	Pathogenic	0.67
Sift	Benign	0.055	T;T;.
Sift4G	Uncertain	0.013	D;D;D
Polyphen		0.98	D;D;D
Vest4		0.82
MutPred		0.79		Loss of catalytic residue at Y1305 (P = 0.2223);.;Loss of catalytic residue at Y1305 (P = 0.2223);
MVP		0.64
MPC		0.87
ClinPred		0.97	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.85
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs868064117; hg19: chr12-123782650;